San Antonio, TX—Adding the PD-L1 inhibitor atezolizumab (Tecentriq) to nab-paclitaxel (Abraxane) chemother­apy is the first immunotherapy-based combination to improve progression-free survival (PFS) and overall survival (OS) in women with advanced or metastatic triple-negative breast cancer and PD-L1 expression compared with placebo plus nab-paclitaxel, according to results of the IMpassion130 clinical trial.

“These are brand-new data. There is no treatment effect in PD-L1–negative patients, and the survival curves are superimposable,” Dr Emens added.

The IMpassion130 Study

An exploratory analysis of the IMpassion130 study provided important news that patients with PD-L1–negative disease who were enrolled in the trial had no survival benefit from the immunotherapy plus chemotherapy combination.

These findings support the use of atezolizumab plus nab-paclitaxel exclusively in patients with PD-L1–positive triple-negative breast cancer and strongly suggest that all patients with metastatic triple-negative breast cancer be tested for PD-L1 expression before treatment selection, according to experts who were interviewed for this article.

The median PFS was identical (5.6 months) in both arms of the study in patients with PD-L1–negative disease. By contrast, PFS was significantly improved with the addition of immunotherapy in the PD-L1–positive patients versus placebo.

The median OS was similar in both study arms in patients without PD-L1 expression—18.9 months with the immunochemotherapy combination and 18.4 months with placebo plus nab-­paclitaxel. By contrast, in patients with PD-L1–positive disease, a 10-month OS advantage was seen in the immunotherapy arm versus the placebo plus nab-­paclitaxel arm (median, 25.5 months vs 15.5 months, respectively).

The majority of patients who had PD-L1–positive disease had PD-L1 expression on immune cells; only 2% had PD-L1 expression on tumor cells.

The threshold for benefit from the addition of immunotherapy was PD-L1 expression of ≥1% in immune cells. Patients whose tumors expressed CD8+ T-cells and stromal tumor-infiltrating lymphocytes, as well as patients with a BRCA mutation, benefited from the immunochemotherapy combination only if they also had PD-L1–positive disease.

“As long as the immune cells express PD-L1 of 1% or more, patients will benefit from atezolizumab plus nab-paclitaxel,” Dr Emens said. “The takeaway message is that higher levels of PD-L1 are not better. All levels of PD-L1 expression benefited. PD-L1 expression on tumor cells did not provide additional information beyond PD-L1 expression on immune cells.”

Based on the results of the IMpassion130 clinical trial, on March 8, 2019, the FDA approved the combination of atezolizumab with nab-paclitaxel for the treatment of unresectable locally advanced or metastatic triple-negative breast cancer in patients with PD-L1 expression, as determined by the FDA-approved test, VENTANA PD-L1 (SP142) Assay, which was approved on the same day.